Title: Differential regulation of chemokine production by Fc gamma receptor engagement in human monocytes: association of CCL1 with a distinct form of M2 monocyte activation (M2b, type 2)
Authors: Sironi, Marina ×
Martinez, Fernando O
D'Ambrosio, Daniele
Gattorno, Marco
Polentarutti, Nadia
Locati, Massimo
Gregorio, Andrea
Lellem, Andrea
Cassatella, Marco A
Van Damme, Jozef
Sozzani, Silvano
Martini, Alberto
Sinigaglia, Francesco
Vecchi, Annunciata
Mantovani, Alberto #
Issue Date: Aug-2006
Publisher: Liss
Series Title: Journal of Leukocyte Biology vol:80 issue:2 pages:342-349
Abstract: CC chemokine ligand 1 (CCL1; I-309) is a CC chemokine that interacts with CC chemokine receptor 8, which is preferentially expressed in polarized T helper cell type 2 and Tc2 cells, in eosinophils, and in T regulatory cells. The present study, prompted by transcriptional profiling of human monocytes undergoing different forms of activation, was designed to characterize the production of CCL1 in monocytes compared with the production of other chemokines (CCL2, CCL22, and CCL18) differentially regulated by distinct activation signals. Lipopolysaccharide (LPS), interferon-gamma (IFN-gamma), interleukin (IL)-1 beta, tumor necrosis factor alpha, IL-4, IL-13, IL-10, IL-6, IL-18, and combinations thereof did not induce CCL1 production in monocytes, and some of these signals stimulated production of reference chemokines. Induction of CCL1 in monocytes required engagement of Fe receptor for immunoglobulin G (Fc gamma R)II and exposure to IL-1 beta or LPS. This combination of stimuli results in a form of M2 (M2b, Type 2) macrophage activation. Fc gamma R engagement also induced CCL22 and amplified its stimulation by IL-4. In contrast, Fc gamma R stimulation inhibited the IL-10- and LPS-mediated induction of CCL18. IL-10, IL-4, and IFN-gamma inhibited induction of CCL1 by Fc gamma R ligation and IL-1 beta. CCL1 was present in synovial fluids and macrophages in juvenile idiopathic arthritis. Thus, regulation of CCL1 in human monocytes is unique, with an obligate requirement of Fc gamma R engagement and costimulation by signals (IL-1 beta and LPS), which use the myeloid differentiation primary-response protein 88 adaptor protein. Thus, CCL1 is a CC chemokine with a unique pattern of regulation associated with a distinct form of M2 (Type 2, M2b) monocyte activation, which participates in macrophage-dependent regulatory circuits of innate and adaptive immunity. J. Leukoc. Biol. 80: 342-349; 2006.
ISSN: 0741-5400
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Molecular Immunology (Rega Institute)
× corresponding author
# (joint) last author

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